This is an interdisciplinary program designed to define, diagnose and understand the genetic and environmental influences on cranialfacial malformations. The objective of this program is to investigate regulatory control mechanisms operating during critical stages of oral-facial cranial development, as well as during subsequent postnatal growth, maturation and senescence. Significant processes associated with normal and abnormal cephalogenesis are defined into problems of (1) transcriptional controls, (2) translational controls, (3) cell-cell interactions, (4) tissue-tissue interactions, (5) specific organ-tissue interactions, (6) hormone-cell interactions, (7) neurological-tissue interactions, and (8) maternal-zygote to maternal-fetus interactions. Genetic, biochemical, immunological, morphological and physiological criteria will be integrated in order to implement our research program design. The solution to problems will be sought at multiple levels of biological organization (molecular, cellular, tissue, humoral, organ, and organism). The research activities are basic, interdependent and unified into the central theme of this program project.